Catalytic hydrogenation processes

ABSTRACT

Catalysts of formula
 
[Ru(L) m (L′) w XY]  (II)
 
wherein X and Y represent simultaneously or independently a hydrogen or halogen atom, a hydroxy group, or an alkoxy, carboxyl or other anionic radical, m is 1 or 2, w is 1 when m is 1 and w is 0 when m is 2, L is a phosphino-amine or phosphino-imine bidentate ligand and L′ a diphosphine, are useful for the hydrogenation of substrates having a carbon-hetero atom double bond.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of application Ser. No. 10/380,483 filed Sep. 3, 2003, now U.S. Pat. No. 7,317,131, which is the 371 filing of International Application PCT/IB01/01657 filed Sep. 11, 2001, which claims the benefit of International Application PCT/IB00/01303 filed Sep. 13, 2000 and U.S. provisional application 60/232,144 filed Sep. 13, 2000. The entire content of each prior application is expressly incorporated here by reference.

TECHNICAL FIELD

The present invention relates to the field of catalytic hydrogenation and, more particularly, to the use of metal complexes with P—N bidentate ligands in hydrogenation processes for the reduction of compounds containing a carbon-heteroatom double bond.

PRIOR ART

Reduction of carbon-heteroatom double bond groups such as ketone, aldehyde or imine groups, is one of the fundamental reactions in chemistry, and is used in a large number of chemical processes.

Several different kinds of processes are known to achieve such transformation, and they can be classified in four main types according to the nature of the reducing system:

-   a) enzymatic processes, in which an enzyme is used to catalyze the     reduction -   b) hydride processes, in which a hydride metal salt such as LiAlH₄     is used -   c) hydrogen transfer processes, in which hydrogen-donors such as     secondary alcohols and in particular isopropanol (^(i)PrOH) are used -   d) hydrogenation processes, in which molecular hydrogen is used.

However, from a practical point of view, the industrial application of the first two methods is difficult since the use of enzymes is delicate and can limit the structure of the compound that can be reduced. On the other hand, hydride processes require the use of highly reactive, hazardous and expensive hydrides.

Both hydrogen transfer and hydrogenation processes need a catalyst or catalytic system (e.g. a pre-catalyst) to activate the reducing agent, namely an alcohol or molecular hydrogen respectively.

Despite the fact that many catalysts for the reduction of a carbon-heteroatom double bond by hydrogen transfer are already known, hydrogen transfer processes are still of difficult application for industrial purposes since they need very large volumes of solvents as reducing agents and high catalyst loadings.

From a practical point of view, hydrogenation processes are more attractive as they use cheap hydrogen gas and can be run out in the presence of a small quantity or even in the absence of solvent, in contrast to the hydrogen transfer processes, which need large volumes of solvent as reductant. However, the former process implies the activation of molecular hydrogen, which is more difficult to achieve than the activation of an alcohol.

For a long time the development of useful catalysts for the hydrogenation of carbon-heteroatom double bonds has been an unachieved goal in chemistry, and it was only recently that several new catalysts for the hydrogenation of ketones have been developed.

The hydrogenation catalysts for simple ketones reported up to now have the same general formula, always including a ruthenium atom coordinated by a bidentate ligand and two monodentate phosphines or amines, or two bidentate ligands. The bidentate ligands are always a diphosphine (P—P) or a diamine (N—N), and the metal centre is always coordinated to two phosphorous atoms and two nitrogen atoms. Very efficient pre-catalysts are those of the formula [Ru(P—P)(N—N)Cl₂] (see R. Noyori et al., in Angew.Chem.Int.Ed., 2001, 40, 41; Morris et al. in Organometallics, 2000, 19, 2655; or Takasago EP 0901997 and JP 11189600).

From the examples cited herein above, one can notice that the catalysts reported up to now exhibit little diversity of the ligand structure and coordination spheres around the metal center. As a consequence of such little diversity, the tuning of the activity and of the performance of the hydrogenation process is not easy. Additionally, these catalysts generally need the use of ligands such as BINAP or sophisticated chiral diamines which require themselves a long, difficult and tedious synthesis.

Therefore, there is a need for hydrogenation processes using catalysts or pre-catalysts with a greater diversity in the ligand structures and coordination spheres around the metal center, and implying the use of ligands that are easily and readily obtained.

DESCRIPTION OF THE INVENTION

In order to overcome the problems aforementioned, the present invention relates to new processes for the reduction by hydrogenation of compounds containing a carbon-heteroatom double bond wherein metal complexes with P-N bidentate ligands are usefully used as catalysts or as pre-catalysts.

The invention concerns a process for the hydrogenation, using molecular hydrogen (H₂), of a C═O or C═N double bond of a substrate into the corresponding hydrogenated compound, in the presence of a catalyst or pre-catalyst (hereinafter referred to as “complex” unless specified otherwise) and a base.

More particularly, typical substrates that can be reduced by the process of the invention are of formula

wherein W is an oxygen atom or a NR group, R being a hydrogen atom, a hydroxy radical, a C₁ to C₈ cyclic, linear or branched alkyl or alkenyl group, possibly substituted, or an aromatic ring, possibly substituted; and R^(a) and R^(b) represent simultaneously or independently a hydrogen, an aromatic group possibly substituted, a cyclic, linear or branched alkyl or alkenyl group, possibly substituted, or a heterocyclic group possibly substituted; or two of symbols R^(a), R^(b) and R, taken together, form a ring, possibly substituted, and provide the corresponding hydrogenated compound of formula

wherein W, R^(a) and R^(b) are defined as in formula (I).

Possible substituents of R^(a), R^(b) and R are halogen atoms, OR^(c), NR^(c) ₂ or R^(c) groups, in which R^(c) is a hydrogen atom or a C₁ to C₁₀ cyclic, linear or branched alkyl or alkenyl group.

Since R^(a) and R^(b) may be different, it is hereby understood that the final product of formula (I′) may be chiral, thus possibly consisting of a practically pure enantiomer or of a mixture of stereoisomers, depending on the nature of the catalyst used in the process.

Preferred substrates are the imines (W═NR), ketones or aldehydes (W═O) that will provide respectively an amine or alcohol, which are useful in the pharmaceutical, agrochemical or perfumery industries as final product or as an intermediate.

Particularly preferred substrates are the ketones or aldehydes that will provide an alcohol which is useful in the perfumery industry, as final product or as an intermediate. Also particularly preferred substrates are the imines that will provide an amine, particularly useful in the pharmaceutical or agrochemical industries, again as final product or as an intermediate.

The processes of the invention are characterized by the use of a complex of the general formula [Ru(L)_(m)(L′)_(w)XY]  (II) wherein X and Y represent, simultaneously or independently, a hydrogen or halogen atom, a hydroxy radical, or a C₁ to C₈ alkoxy or acyloxy radical;

-   m is 1 or 2, w is 1 when m is 1 and w is 0 when m is 2; -   L represents a bidentate N-P ligand of general formula

in which formula (III) the dotted line indicates a single or double bond;

-   n is an integer from 1 to 4; z is 0 or 1 when the carbon-nitrogen     bond with the dotted line represents a double, respectively single     bond; -   R¹ represents a hydrogen atom, a linear, branched or cyclic C₁ to     C₁₀ alkyl or alkenyl group, possibly substituted, a R*CO acyl group,     or a R*SO₂ group, R* representing a C₁ to C₈ alkyl or aryl group; -   R² and R³ represent, simultaneously or independently, a linear,     branched or cyclic C₁ to C₈ alkyl or alkenyl group, possibly     substituted, an aromatic ring, possibly substituted, or an OR^(2′)     or NR^(2′)R^(3′) group, R² and R³ being defined as R² and R³; or     said groups R² and R³ being possibly bonded together to form a     saturated or aromatic ring having 5 to 10 atoms and including the     phosphorous atom to which said R² and R³ groups are bonded; -   R⁴, R⁵, R⁶ and R⁷represent, simultaneously or independently, a     hydrogen atom, a linear, branched or cyclic C₁ to C₁₀ alkyl or     alkenyl group, possibly substituted, an aromatic ring, possibly     substituted, or an OR⁴ or NR^(4′) R^(5′) group, R^(4′) and R^(5′)     being defined as R⁴ and R⁵; or two distinct R⁴ and/or R⁵ groups     being possibly bonded together to form a C₅ to C₈ saturated or     aromatic ring including the carbon atoms to which each of said R⁴ or     R⁵ group is bonded; or R⁶ and R¹ may optionally be bonded together     to form a saturated or unsaturated heterocycle, possibly substituted     and possibly containing other heteroatoms, having 5 to 10 atoms and     including the carbon atom and the N atom of the bond indicated by     the dotted line; and -   L′ represents a bidentate P—P ligand of formula

wherein R² and R³ are defined as in formula (III), and Q represents a linear or cyclic C₂-C₇ alkylene radical, possibly substituted, a metallocenediyl or a C₆-C₂₂ arylene or biaryldiyl radical, possibly substituted.

Possible substituents of R¹ to R⁷ and Q are C₁ to C₁₀ alkoxy or polyalkyleneglycol groups, carboxylic esters, C₁ to C₆ alkyl groups, or C₅ to C₁₂ cycloalkyl or aromatic groups.

The ligands L and L′ may be chiral or achiral. Therefore, the invention may provide complexes of formula (II) useful in asymmetric hydrogenations.

In a preferred embodiment of formula (II), X and Y represent, simultaneously or independently, a hydrogen or chlorine atom, a hydroxy radical, a C₁ to C₆ alkoxy radical, such as a methoxy, ethoxy or isopropoxy radical, or a C₁ to C₆ acyloxy radical such as a CH₃COO or CH₃CH₂COO radical;

-   m is 1 or 2, w is 1 when m is 1 and w is 0 when m is 2; -   L represents a bidentate N—P ligand of general formula

in which n is an integer from 1 to 3;

-   R¹ represents a hydrogen atom, a linear, branched or cyclic C₁ to C₆     alkyl or alkenyl group, possibly substituted; -   R² and R³represent, simultaneously or independently, a linear,     branched or cyclic C₂ to C₆ alkyl group, possibly substituted, an     aromatic ring, possibly substituted; or said groups R² and R³ being     possibly bonded together to form a saturated or aromatic ring having     5 to 6 atoms and including the phosphorous atom to which said R² and     R³ groups are bonded; -   R⁴, R⁵, R⁶ and R⁷ represent, simultaneously or independently, a     hydrogen atom, a linear or branched C₁ to C₄ alkyl group, possibly     substituted, or an aromatic ring possibly substituted; or two     distinct R⁴ and/or R⁵ groups being possibly bonded together to form     a C₅ to C₆ saturated or aromatic ring including the carbon atoms to     which each of said R⁴ or R⁵ group is bonded; or R⁶ and R¹ may     optionally be bonded together to form a saturated heterocycle,     possibly substituted and possibly containing other heteroatoms,     having 5 to 6 atoms and including the carbon atom and the N atom of     the bond indicated by the dotted line; and -   L′ represents a bidentate P—P ligand of formula (IV) wherein R² and     R³ are defined as in formula (III′), and Q represents a linear C₂-C₅     alkylene radical, possibly substituted, a ferrocenediyl or a     biphenyldiyl or binaphthyldiyl radical, possibly substituted.

Possible substituents of R¹ to R⁷ and Q are C₁ to C₅ alkoxy or polyalkyleneglycol groups, carboxylic esters, C₁ to C₄ alkyl groups, or C₅ to C₁₀ cycloalkyl or aromatic groups.

In an alternative preferred embodiment of the complexes of formula (II), X and Y represent, simultaneously or independently, a hydrogen or chlorine atom, a hydroxy radical, a C₁ to C₆ alkoxy radical, such as a methoxy, ethoxy or isopropoxy radical, or a C₁ to C₆ acyloxy radical such as a CH₃COO or CH₃CH₂COO radical;

-   m is 1 or 2, w is 1 when m is 1 and w is 0 when m is 2; -   L represents a bidentate N—P ligand of general formula

in which G represents a group of formula R⁶C═NR¹ or a C═N function-containing heterocycle, possibly substituted and possibly containing other heteroatoms, such as a 2-pyridyl, a 1-oxazolinyl, a 2-imidazolyl or a 2-isoquinolinyl group;

-   R⁶ represents a hydrogen atom, a linear or branched C₁ to C₄ alkyl     group, possibly substituted, or an aromatic ring possibly     substituted; -   n, R¹, R², R³, R⁴, R⁵ are defined as in formula (III′); and -   L′ represents a bidentate P-P ligand of formula (IV) wherein R² and     R³ are defined as in formula (III′), and Q represents a linear C₂-C₅     alkylene radical, possibly substituted, a ferrocenediyl or a     biphenyldiyl or binaphthyldiyl radical, possibly substituted.

Possible substituents of R¹ to R⁶, Q and G are C₁ to C₅ alkoxy or polyalkyleneglycol groups, carboxylic esters, C₁ to C₄ alkyl groups, or C₅ to C₁₀ cycloalkyl or aromatic groups.

Particularly advantageous when used in the processes of the invention are the complexes of formula [Ru(L)₂XY]  (II′) wherein X and Y represent, simultaneously or independently, a hydrogen or chlorine atom, a methoxy, ethoxy or isopropoxy radical, or a CH₃COO or CH₃CH₂COO radical; and

-   L is a ligand of formula (V) or (V′)

wherein the dotted lines in formula (V′) indicate the presence of a phenyl or a naphthyl group;

-   b represents 1 or 2; -   G′ represents a R⁶C═NR¹ group or a C═N function-containing     heterocycle, possibly substituted and possibly containing other     heteroatoms, such as a 2-pyridyl, an 2-isoquinolinyl, an     1-oxazolinyl, or a 2-imidazolyl group; -   R¹ represents a hydrogen atom or a C₁ to C₄ linear or branched alkyl     group, possibly substituted; -   R² and R³ represent a linear, branched or cyclic C₂ to C₆ alkyl     group or an aromatic ring, possibly substituted; and -   R⁶ represents a hydrogen atom, a linear or branched C₁ to C₄ alkyl     group, possibly substituted, or an aromatic ring, possibly     substituted.

Possible substituents of R¹ to R³, R⁶ and G′ are C₁ to C₅ alkoxy or polyalkyleneglycol groups, C₁ to C₄ alkyl groups, or C₅ to C₁₀ cycloalkyl or aromatic groups.

In an alternative embodiment of the complexes of formula (II′), L is a ligand of formula (VI) or (VI′)

wherein the dotted lines in formula (VI′) indicate the presence of a phenyl or a naphthyl group;

-   R¹, R², R³, and b are defined as in formula (V) or (V′); and -   R⁶ and R⁷ represent, simultaneously or independently, a hydrogen     atom, a linear or branched C₁ to C₄ alkyl group, possibly     substituted, or an aromatic ring possibly substituted; or R⁶ and R¹     may optionally be bonded together to form a saturated heterocycle,     possibly substituted and possibly containing other heteroatoms, such     as a 2-pyrrolidine, a 2-piperidine or a 2-morpholine heterocycle.

Possible substituents of R¹ to R³, R⁶ and R⁷ are C₁ to C₅ alkoxy or polyalkyleneglycol groups, C₁ to C₄ alkyl groups, C₅ to C₁₀ cycloalkyl or aromatic groups.

Moreover, in the processes of the invention, it is possible to use in a particularly advantageous manner the complexes of formula [Ru(L)₁(L′)₁XY]  (II″) wherein X and Y represent, simultaneously or independently, a hydrogen or chlorine atom, a methoxy, ethoxy or isopropoxy radical, or a CH₃COO or CH₃CH₂COO radical;

-   L′ is a bidentate P—P ligand of formula (IV) wherein R² and R³ are     defined as in formula (V), and Q represents the butane-1,4-diyl     radical, possibly substituted, a ferrocenediyl or a binaphthyldiyl     radical, possibly substituted; and -   L is a ligand of formula (VI) or (VI′).

Possible substituents of Q are C₁ to C₅ alkoxy or polyalkyleneglycol groups, C₁ to C₄ alkyl groups, or C₅ to C₁₀ cycloalkyl or aromatic groups.

In an alternative preferred embodiment of the complexes of formula (II″), L is a ligand of formula (V) or (V′).

The complexes of formula (II′) or (II″) are, to the best of our knowledge, new compounds and therefore are also part of the invention.

Many of the ligands described above are known in the art and, unless specified differently in the examples, they are obtained according to methods described in the literature. The ligands that are new can be obtained by modifying known procedures according to the general knowledge of a person skilled in the art. Some references are cited in the examples.

The complexes used in the processes of the invention can be prepared in situ in the hydrogenation reaction medium, without isolation or purification, just before their use. Alternatively, they can be isolated before use. The experimental procedure for their synthesis is substantially similar in both cases. Furthermore, they can also be prepared and stored in solution, the latter being stable for many days.

Said complexes can be prepared according to methods similar to those described in the literature, e.g. by Noyori et al. in JP 11189600, or in Angew. Chem. Int. Ed. 1998, 37, 1703-1707, or by Yang et al. in C.R.Acad.Sci., Ser.IIc: Chim. 1999, 2, 251, or yet by Quirmbach et al. in Tetrahedron, 2000, 56, 775

As previously mentioned, the complexes can be prepared in situ, in the hydrogenation medium, by several methods without isolation or purification, just before their use. We have established that one of the possible procedures to advantageously prepare in situ a complex of formula (II) consists in reacting an appropriate Ru complex of formula [Ru(“diene”)(“allyl”)₂] in which “diene” represents a cyclic or linear hydrocarbon containing two carbon-carbon double bonds, conjugated or not, such as for example 1,5-cyclooctadiene (COD) or 1,3-butadiene, and “allyl” represents a linear or branched C₃ to C₈ hydrocarbon radical containing one carbon-carbon double bond, such as for example the allyl (CH₂CHCH₂) or methylallyl (CH₂CCH₃CH₂) group, with a non-coordinating acid such as HBF₄.Et₂O, preferably one equivalent in respect to the metal, then treating the resulting solution with the desired amount of a ligand L, and if necessary of ligand L′, as defined previously, and finally treating the thus obtained mixture with a base in the presence of a primary or secondary alcohol.

Preferably the [Ru(diene)(allyl)₂] is [Ru(COD)(allyl)₂] or [Ru(COD) (methylallyl)₂].

Another procedure to advantageously prepare in situ a complex of formula (II) consists in reacting a ruthenium complex of formula [Ru(C₆H₆)(Cl)₂]₂ with a required amount of ligand L, and if necessary of ligand L′, as defined previously, and then treating the thus obtained reaction mixture with a base, in the presence of an alcohol.

In any case, and independently of the procedure chosen to prepare the complex in situ, the base used is, preferably, the same base used in the process of the invention.

As previously mentioned, the complexes of formula (II), (II′) or (II″) are very useful for the reduction by hydrogenation of compounds containing a carbon-heteroatom double bond. A typical process implies the mixture of the substrate with a complex of formula (II), (II′) or (II″), in the presence of a base and optionally a solvent, and then treating such a mixture with molecular hydrogen at a chosen pressure and temperature.

The complexes used in the processes of the invention, an essential parameter of the process, can be added to the reaction medium in a large range of concentrations. As non-limiting examples, one can cite as complex concentration values ranging from 0.1 ppm to 50000 ppm, relative to the amount of substrate, thus representing respectively a substrate/complex (S/com) ratio of 10⁷ to 20. Preferably, the complex concentration will be comprised between 0.1 and 5000 ppm, i.e. a S/com ratio of 107 to 200 respectively. More preferably, there will be used concentrations in the range of 0.5 to 1000 ppm, corresponding to a S/com ratio of 2×10⁶ to 1000 respectively. It goes without saying that the optimum concentration of complex will depend on the nature of the latter and on the pressure of H₂ used during the process.

As mentioned previously the process of the invention is performed in the presence of a base.

Said base can be the substrate itself, if the latter is basic, or any conventional base. One can cite, as non-limiting examples, organic non-coordinating bases such as DBU, an alkaline or alkaline-earth metal carbonate, a carboxylate salt such as sodium or potassium acetate, or an alcoholate or hydroxide salt. Preferred bases are the alcoholate or hydroxide salts selected from the group consisting of the compounds of formula (R⁸O)₂M′ or R⁸OM″, wherein M′ is an alkaline-earth metal, M″ is an alkaline metal and R⁸ stands for hydrogen or a C₁ to C₆ linear or branched alkyl radical.

Useful quantities of base, added to the reaction mixture, may be comprised in a relatively large range. One can cite, as non-limiting examples, ranges comprised between 0.5 to 90000 molar equivalents, relative to the complex (e.g. base/complex=0.5 to 90000), preferably 5 to 10000, and even more preferably between 10 and 5000 molar equivalents. However, it should be noted that, depending on the substrate and the complex structure, it is also possible to add a small amount of base (e.g. base/complex=1 to 5) to achieve high hydrogenation yields.

The hydrogenation reaction can be carried out in the presence or absence of a solvent. When a solvent is required or used for practical reasons, then any solvent current in hydrogenation reactions can be used for the purposes of the invention. Non-limiting examples include aromatic solvents such as benzene, toluene or xylene, hydrocarbon solvents such as hexane or cyclohexane, ethers such as tetrahydrofuran, or yet primary or secondary alcohols, or mixtures thereof. A person skilled in the art is well able to select the solvent most convenient in each case to optimize the hydrogenation reaction, however primary or secondary alcohols such as ethanol or isopropanol are the preferred solvents.

In the hydrogenation processes of the invention, the reaction can be carried out at a H₂ pressure comprised between 10⁵ Pa and 80×10⁵ Pa (1 to 80 bars). Again, a person skilled in the art is well able to adjust the pressure as a function of the catalyst load and of the dilution of the substrate in the solvent. As examples, one can cite typical pressures of 1 to 40×10⁵ Pa (1 to 40 bar).

The temperature at which the hydrogenation can be carried out is comprised between 0° C. and 100° C., more preferably in the range of between 20° C. and 40° C. Of course, a person skilled in the art is also able to select the preferred temperature as a function of the melting and boiling point of the starting and final products or of the solvent if present.

Additionally, we surprisingly discovered that in some cases it is possible to successfully hydrogenate some substrates into the corresponding alcohols in the presence of hydrido or diacetato complexes of formula (II′), without a base.

Therefore, the invention concerns also a process for the reduction of an aryl or diaryl ketone into the corresponding alcohol by hydrogenation in the presence of a complex, said process being characterized in that said complex is of formula: [Ru(L)₂XY]  (II′) wherein L is as ligand of formula (V), (V′), (VI) or (VI′); and

-   X represents a hydrogen atom and Y represents a hydrogen or chlorine     atom, a methoxy, ethoxy or isopropoxy radical, or a CH₃COO or     CH₃CH₂COO radical; or X and Y represent a hydrogen atom or a CH₃COO     or CH₃CH₂COO radical.

Said processes are typically performed by admixing the substrate with a complex of formula (II′), as herein above defined, optionally in presence a solvent, and then treating such a mixture with molecular hydrogen at a chosen pressure and temperature. The concentration of the complex relative to the substrate, the nature of the optional solvent, the H₂ pressure and the temperature of the process are as previously described.

The invention will now be described in further detail by way of the following examples, wherein the temperatures are indicated in degrees centigrade and the abbreviations have the usual meaning in the art.

All the procedures described hereafter have been carried out under an inert atmosphere unless stated otherwise. Hydrogenations were carried out in open glass tubes placed inside a stainless steel autoclave or in Schlenk flasks. H₂ gas (purity: 99.99% or more) was used as received. All substrates and solvents were distilled from appropriate drying agents under Ar. NMR spectra were recorded on Bruker instruments (¹H at 400.1 MHz, ¹³C at 100.6 MHz, and ³¹P at 121.4, 145.8 or 161.9 MHz) and normally measured at 300 K. Chemical shifts are listed in ppm.

EXAMPLE 1 Preparation of Some Ru Complexes of the Formula (II)

TABLE 1 Structure of the ligands of formula (IV) or (VI) used for the synthesis of the corresponding complexes structure name

(VI)-1

(VI)-2

(VI)-3

(IV)-1

(IV)-2

(IV)-3 Ligand (VI)-1 is commercially available from FLUKA. Ligands (VI)-2 and (VI)-3 were obtained from the corresponding amino-acids according to the procedure described in K. Kashiwabara, et. al.; Bull. Chem. Soc. Jpn., 1981, 54, 725; S. Sakuraba, et. al.; Chem. Pharm. Bull., 1995, 43, 927; A. Saitoh, et. al.; Synlett., 1999, 4, 483; A. Saitoh, et. al.; J. Org. Chem., 2000, 65, 4227. Ligands (IV)-1, 2, 3 are commercially available from Aldrich Chemical Company a) Preparation of the Complex [RuHCl((VI)-1)₂]:

Isopropanol (5 ml) was added to a mixture of [RuCl₂(COD)]_(n) (300 mg, 1.07 mmol of Ru), NaOH (200 mg, 5.0 mmol) and (VI)-1 (510 mg, 2.2 mmol) under a flow of argon, and the resulting suspension stirred for 6 hours, during which a bright yellow precipitate formed. Water (30 ml) was added and the mixture was stirred for another hour. It was then filtered using a schlenk sintered glass frit, washed with water (3×10 ml) and vacuum dried. Recrystallization from toluene/hexanes afforded a pure sample of the complex. Yield=386 mg, 60%.

¹H NMR (C₆D₆): −19.83 (t, ²J_(HP)=25.9 Hz, 1H, RuH); 2.18-4.54 (m, 12H); 6.90-7.38 (m, 20H, Ph).

³¹P{¹H} NMR (C₆D₆): 77.8 (s).

IR (Nujol): 1924 cm⁻¹ (vRuH), 3282, 3141 cm⁻¹ (vNH).

b) Alternative Preparation of the Complex [RuHCl((VI)-1)₂]:

A solution of [RuHCl(Ph₃P)₃] (obtained as described by Schunn et al. in Inorg.Synth., 1970, 131) (1002 mg, 1.00 mmol) and (VI)-1 (458 mg, 2.00 mmol) in toluene (40 mL) was stirred and heated to 40° C. for 24 h and then for another 2 h at 100° C. Then, about half of the solvent was stripped off under vacuum from the yellow suspension, and the yellow precipitate then directly collected by filtration at ambient temperature. The filtrate was washed with pentanes and dried in vacuum to give 520 mg of [RuHCl(VI)-1)₂] (0.87 mmol, yield=87%).

¹H NMR (d₈-THF): −19.3 ppm (t, J=26.4 Hz, hydride);

¹H NMR (d₆-DMSO): −10.9 ppm (t, J=25.2 Hz, hydride);

³¹P{¹H} NMR (d₈-THF): 83.2 ppm (s);

³¹P{¹H} NMR (d₆-DMSO): 71.9 ppm (s).

c) Preparation of the Complex [RuCl₂((VI)-1)₂]:

A 50 mg sample of [RuHCl((VI)-1)₂] was dissolved in methylene chloride (1.0 ml) and the resulting solution was allowed to stand at room temperature for 24 hours. A bright yellow precipitate was obtained upon addition of diethyl ether (2 ml).

Yield=43 mg, 81%.

¹H NMR (CD₂Cl₂): 1.68-3.72 (m, 12H); 6.99-7.17 (m, 20H, Ph).

³¹P{¹H} NMR(CD₂Cl₂): 62.51 (s).

d) Alternative Preparation of the Complex [Ru(Cl)₂((VI)-1)₂]:

Toluene (5 ml) was added to a mixture of [RuCl₂(COD)]_(n) (300 mg, 1.07 mmol) and (VT)-1 (510 mg, 2.2 mmol) and the resulting suspension refluxed for 12 hours under argon, during which a bright yellow precipitate formed. The mixture was cooled to room temperature and the solids filtered, washed with toluene (3×5 ml), then ether (3×5 ml) and vacuum dried.

Yield=582 mg, 91%.

¹H NMR (CD₂Cl₂): 1.68-3.72 (m, 12H), 6.99-7.17 (m, 20H, Ph).

³¹P{¹H} NMR(CD₂Cl₂): 62.51.

e) Preparation of the Complex [RuHCl((VI)-2)₂]:

This complex was prepared using a similar procedure to that described in a) or in b).

Yield=67% for method a).

¹H NMR (C₆D₆): −19.15 (t, ²J_(HP)=25.4 Hz, 1H, RuH); 1.01-4.54 (m, 16H); 6.93-7.76 (m, 20H, Ph).

³¹P {¹H} NMR (C₆D₆): 72.9 (d), 72.4 (d, ²J_(PP)=34.8 Hz).

f) Preparation of the Complex [RuCl₂((VI)-2)₂]:

This complex was prepared using a similar procedure to that described in d) or in c). Yield=83% for method c.

¹H NMR (C₆D₆): 1.01-3.68 (m, 16H); 6.87-62 (m, 20H, Ph). ³¹P {¹H} NMR (C₆D₆): 57.5(s).

g) Preparation of the Complex [RuHCl((VI)-3)₂]:

This complex was prepared using a similar procedure to that described in a) or in b) and resulted in a mixture of diastereomers. However, the isolated solid was effectively used as a catalyst precursor in the ketone hydrogenation.

h) Preparation of the Complex [RuHCl((IV)-2)((VI)-1)]:

A mixture of [RuHCl(IV-2)(PPh₃)] (300 mg, 0.29 mmol) (obtained according to Abdur-Rashid, K. et al. in Organometallics 2001, 20, 1047) and (VT)-1 (70 mg, 0.30 mmol) in toluene (5 ml) was refluxed for 6 hours. The resulting solution was concentrated to 1 ml and hexanes (10 ml) added, resulting in a bright yellow product. Yield=261 mg, 90%.

¹H NMR (C₆D₆): −17.75 ppm (dt, ²J_(HP)=20.6, 25.6 Hz, 1H, RuH), 0.95-3.68 ppm (m, 6H), 6.22-8.83 ppm (m, 42H);

³¹P{¹H} (C₆D₆): 38.1 ppm (dd, ²J_(PP)=292, 32.5 Hz), 40.6 ppm (dd, ²J_(PP)=292, 31.4 Hz), 67.5 ppm (dd, ²J_(PP)=32.5, 31.4 Hz)

IR (Nujol): 1986 cm⁻¹ (vRuH); 3329, 3259 cm⁻¹ (vNH).

i) Preparation of the Complex [RuHCl((IV)-2)((VI-2)]:

This complex was prepared using a similar procedure to that described in h). Yield=272 mg, 93%.

¹H NMR (C₆D₆): −17.36 ppm (ddd, ²J_(HP)=21.7, 21.0, 20.1 Hz, 1H, RuH), 0.85-3.00 ppm (m, 8H), 6.22-6.88 ppm (m, 42H);

³¹P {¹H} NMR (C₆D₆): 29.43 ppm (dd, 2J_(PP)=294, 31.2 Hz), 32.9 ppm (dd, ²J_(PP)=294, 32.4 Hz), 63.4 ppm (dd, ²J_(PP)=31.2, 32.4 Hz).

IR (Nujol): 2006 cm⁻¹ (vRuH), 3320, 3250 cm⁻¹ (vNH).

j) Preparation of the Complex [RuHCl((IV)-1)((VI)-1)]:

Synthesis of the precursor [RuHCl((IV)-1)(PPh₃)]: THF (20 mL) was added to a mixture of (IV)-1 (2.0 g, 3.6 mmol) and RuHCl(PPh₃)₃ (3.3 g, 3.4 mmol) and the resulting suspension was refluxed for 6 h under Ar. The solution was then evaporated to dryness under vacuum and the residue was extracted with CH₂Cl₂ (2×15 ml) and filtered. The filtrate was evaporated to dryness and ether (20 ml) was added to the residue. The suspension was stirred for one hour under N₂. The red-brown solids were filtered, washed with ether (2×5 ml) and dried under vacuum. Yield=2.46 g, 72%.

¹H NMR (C₆D₆): 6.9-8.0 ppm (m, 35H, PC₆H₅), 4.56, 4.41, 3.94, 3.78 (br, each 2H, PC₅H₄), −19.52 (dt, ²J_(HP)=19.2, ²J_(HP)=30.6 Hz, RuH).

¹P{¹H} NMR (C₆D₆): 44.79 ppm (t, ²J_(PP)=131 Hz, PPh₃), 68.25 (br, 2 PC₅H₄).

Synthesis of the title complex: A solution of (VT)-1 (240 mg, 1.03 mmol) in THF (5 ml) was added to [RuHCl((IV)-1)(PPh₃)] (950 mg, 1.0 mmol) and the resulting solution stirred for two hours at 20° C. The solvent was removed under vacuum and the solids extracted with THF (3.0 ml) and filtered. Hexane (20 ml) was added to the filtrate, yielding a pale yellow solid, which was filtered, washed with hexane (2×5 ml) and dried under vacuum. Yield=623 mg, 67%.

This exists as two diastereomers in the ratio 2:1:

¹H NMR (C₆D₆): −17.91 ppm (dt, ²J_(HP)=20.2, 26.0 Hz, 1H, RuH of both diastereomers), 1.6-3.4 (several m, 6H dppea), 3.70, 3.75, 3.85, 3.90, 4.09, 4.21, 4.31, 4.60, 5.30 (several m, 8H, PC₅H₄), 6.6-8.6 (several m, 30H);

Diastereomer 1:

³¹P {¹H} NMR (C₆D₆): 58.4 ppm (dd of AMN, 2J_(PP)=31 (AM), 35 (AN) Hz), 52.4 (dd of AMN, ²J_(PP)=286 (MN), 31 (AM) Hz), 47.7 (dd of AMN, ²J_(PP)=286 (MN), 35 (AN) Hz).

Diastereomer 2:

³¹P {¹H} NMR (C₆D₆): 36.8 ppm (dd of AMN, 2J_(PP)=32 (AM), 30 (AN) Hz), 33.0 (dd of AMN, ²J_(PP)=333 (MN), 32.3 (AM) Hz), 27.4 (dd of AMN, ²J_(PP)=333 (MN), 30.5 (AN) Hz).

k) Preparation of the Complex RuHCl((IV)-3)((VI)-1):

Synthesis of the precursor [RuHCl((IV)-3)(PPh₃)_(n)], n=1, 2: THF (20 ml) was added to a mixture of (IV)-3 (1.29 g, 2.6 mmol) and RuHCl(PPh₃)₃ (2.36 g, 2.6 mmol) and the suspension refluxed for 6 h under Ar. The solvent was removed under vacuum and the solids extracted with THF (10 ml) and filtered. The filtrate was evaporated to dryness and a mixture of ether/hexane (1:5) (20 mL) was added. The suspension was stirred vigorously for 2 h. The red-brown solids were filtered off, washed with hexane and dried under vacuum. Yield=1.85 g, 69% (based on a 1:1 mixture of isomers with n=1 and n=2).

Isomer with n=1.

¹H NMR (C₆D₆): −16.72 ppm (dt, ²J_(HP)=22, ²J_(HP)=31 Hz, RuH).

³¹P{¹H} NMR (C₆D₆): 81 ppm (br, P_(A) of AMX), 48 (br m, P_(M) of AMX, ²J_(PP)=242 Hz), 35 (br m, P_(X) of AMX, ²J_(PP)=242).

Isomer with n=2.

¹H NMR (C₆D₆): −17.96 (tt, ²J_(HP)=13.4, ²J_(HP)=28.5 Hz, RuH).

³¹P{¹H} NMR (C₆D₆): 22.8 ppm (t, ²J_(PP)=40.2 Hz), 4.0 ppm (t, ²J_(PP)=40.2 Hz).

Synthesis of the title complex: A solution of (VI)-1 (240 mg, 1.03 mmol) in THF (2.0 ml) was added to 900 mg of [RuHCl((IV)-3)(PPh₃)_(n)] (n=1, 2 in 1:1 ratio) and the mixture was stirred for one hour at 20° C. under N₂. The mixture was filtered and hexanes (20 ml) were added to the filtrate, precipitating a yellow-green solid which was filtered, washed with hexane and dried under vacuum. Yield=582 mg, 76%.

This exists as two diastereomers in a ratio 1.5:1:

Diastereomer 1:

¹H NMR (C₆D₆): −18.1 ppm (dt, ²J_(HP)=19.8, 24.8 Hz, 1H, RuH);

³¹P {¹H} NMR (C₆D₆): 53.3 ppm (dd, ²J_(PP)=28, 280 Hz), 46.3 (dd, ²J_(PP)=28, 31 Hz), 31.4 (dd, ²J_(PP)=280, 31 Hz).

Diastereomer 2:

¹H NMR (C₆D₆): −18.2 (dt, ²J_(HP)=19.8, 24.6 Hz, 1H, RuH);

³¹P {¹H} NMR (C₆D₆): 54.4 ppm (dd, ²J_(PP)=36, 283 Hz), 46.3 (dd, ²J_(PP)=36, 35 Hz), 37.4 (dd, ²J_(PP)=283, 35 Hz).

l) Preparation of the Complex trans-[RuH₂((IV)-2)((VI)-1)]:

Synthesis of precursor [K(18-crown-6)][RuH₃((IV)-2)(PPh₃)]: THF (2 ml) was added to a mixture of [RuHCl((IV)-2)(PPh₃)] (100 mg, 0.10 mmol), KH (20 mg, 0.5 mmol) and 18-crown-6 (26 mg, 0.10 mmol) under an atmosphere of H₂ gas. The mixture was stirred for 5 hours, filtered under a nitrogen atmosphere and hexane (10 ml) added to the filtrate, precipitating a pale red-brown solid. Yield=95 mg, 74%.

¹H NMR (C₆D₆): −9.98 ppm (m, 1H, RuH), −9.36 ppm (m, 1H, RuH), −8.97 ppm (m, 1H, RuH), 3.24 ppm (s, 24H, CH₂), 6.24-8.76 ppm (m, 47H).

³¹P {¹H} NMR (C₆D₆): 59.1 ppm (m), 61.2 ppm (m), 64.7 ppm (m). IR (Nujol): 1799, 1836 cm⁻¹ (vRuH).

Synthesis of the title complex: A mixture of [K(18-crown-6)][RuH₃((IV)-2)(PPh₃)] (100 mg, 77 mmol) and (VI)-1 (20 mg, 86 mmol) in C₆D₆ (0.6 ml) was allowed to stand for 12 hours. The NMR spectrum shows a clean formation of the trans-dihydride complex.

¹H NMR (C₆D₆) Hydride region: −5.16 (m) ppm (m), −6.49 (m).

³¹P {¹H} NMR (C₆D₆): 67.4 (dd), ²J_(PP)=280, 33.4 Hz, 72.8 (dd), ²J_(PP)=280, 38.6 Hz, 81.6 (dd), ²J_(PP)=38.6, 33.4 Hz

m) Preparation of the Complex [Ru(AcO)₂((VI)-1)₂]:

A solution of Ru₂(AcO)₄ (13.1 mg, 0.03 mmol) (prepared according to Lindsay et al. in J.Chem.Soc.Dalton Trans. 1985, 2321) and (VI)-1 (27.5 mg, 0.12 mmol) in CH₂Cl₂ (3 ml) was left for 24 h at ambient temperature. Removal of the solvent in vacuum gave 38 mg of a bright yellow powder. Yield=93%.

³¹P{¹H} NMR (CD₂Cl₂): 50.2(s), 64.8 ppm (s).

EXAMPLE 2 Catalytic Hydrogenation of Ketones Using [RuXY((VI))₂] or [RuXY(VI)(IV)]

Under an atmosphere of hydrogen gas (1-3 atm) at room temperature, catalytic amounts of the complexes with a ligand of formula (VI) described in Example 1, together with 3-10 equivalents of KO^(i)Pr effectively and readily catalyzed the hydrogenation of the neat ketone to the corresponding alcohol. A typical catalytic run using [RuHCl((VI)-2)₂] and acetophenone as substrate is as follows:

-   Acetophenone (2.0 g) was added under a flow of hydrogen gas to a     Schlenk flask containing [RuHCl((VI)-2)₂] (5 mg) and KO^(i)Pr (5     mg). The flask was cooled to liquid nitrogen temperature, filled     with H₂ gas, closed and allowed to gradually warm to room     temperature. The mixture was vigorously stirred for 12 hours. A ¹H     NMR spectrum of the reaction mixture indicated complete conversion     of the ketone to the alcohol. Under these conditions, the complexes     reported in Table 2 resulted in 100% conversion of the ketone to the     corresponding alcohol (Table 2).

TABLE 2 Hydrogenation of ketones using some [RuXY((VI))₂] or [RuXY(VI)(IV)] Test Sub. Complex Com/base Conv.  1 1 [RuHCl((VI)-1))₂] 500/5000 100  1 1 [RuHCl((VI)-1))₂] 500/2500 100  2 1 [RuHCl((VI)-2)₂] 500/2500 100  3 1 [RuHCl((VI)-3)₂] 400/2000 100  4 1 [RuCl₂((VI)-1))₂] 400/2000 100  5 1 [RuCl₂((VI)-2)₂] 400/2000 100  6 1 [RuCl₂((VI)-3))₂] 370/1900 100  7¹⁾ 1 [Ru(AcO)₂((VI)-1))₂] 100/500  100  8 2 [RuCl₂((VI)-1))₂] 240/1200 100  9 2 [RuCl₂((VI)-2)₂] 240/1200 100 10 2 [RuHCl((VI)-1))₂] 240/1200 100 11 2 [RuHCl((VI)-3))₂] 190/1200 100 12 3 [RuCl₂((VI)-1))₂]* 2500/12500 100 13 3 [RuCl₂((VI)-2)₂]* 2500/12500 100 14 3 [RuHCl((VI)-1))₂]* 2500/12500 100 15 3 [RuHCl((VI)-2)₂]* 2500/12500 100 16 4 [RuCl₂((VI)-1)₂] 400/2000 100 17 4 [RuHCl((VI)-1)₂] 400/2000 100 18 4 [RuHCl((VI)-2)₂] 1600/800  100 19 5 [RuHCl((VI)-1))₂] 400/2000 100 20 1 [RuHCl((IV)-2)((VI)-1))] 240/1200 100^(2a)) 21 1 [RuHCl((IV)-2)((VI)-2))] 240/1200 100^(2b)) 22 1 [RuHCl((IV)-3)((VI)-1))] 240/1200 100 23 2 [RuHCl((IV)-2)((VI)-1))] 300/1500 100 24 2 [RuHCl((IV)-2)((VI)-2))] 300/1500 100 25 3 [RuHCl((IV)-1)((VI)-1))] 1750/8500  100 26 3 [RuHCl((IV)-3)((VI)-1))] 1850/8500  100 27 4 [RuHCl((IV)-1)((VI)-1))] 550/2700 100 28 4 [RuHCl((IV)-3)((VI)-1))] 580/2900 100 29 5 [RuHCl((IV)-1)((VI)-1))] 500/2500 100 30 5 [RuHCl((IV)-3)((VI)-1))] 560/2800 100 Sub.: Substrate: 1 = acetophenone, 2 = acetone, 3 = 2,2-dimethyl-1-phenyl-propanone, 4 = 3,3-dimethyl-2-butanone, 5 = 5-hexen-2-one Com/base: molar ratio in ppm relative to the substrate Conv. = conversion (in %, analysed by GC or NMR) of the ketone into the corresponding alcohol (namely 1-phenyl-1-ethanol, isopropanol, 2,2-dimethyl-1-phenyl-propanol, 3,3-dimethyl-2-butanol and 5-hexen-2-ol respectively) after 12 hours. Reaction conditions: H₂ gas (≈3.5 atm.), 20° C. *Hydrogenation performed in 1 g of C₆D₆ for 2.5 g of substrate ¹⁾test performed at 40° C. and under H₂ gas (≈60 atm.), according the hydrogenation conditions described in example 3. ^(2a))e.e. (S enantiomer) = 10%; 2b) e.e. (S enantiomer) = 40%

EXAMPLE 3 Catalytic Hydrogenation of 2-ethyl-4-(2′,2′,3′-trimethyl-3′-cyclopenten-1′-yl)-2-buten-1-al using [RuXY((Vl)-1)₂] or [RuXY((VI)-1)((IV)-4)] prepared in situ

Preparation in situ of a Ru/(VI)-1 solutionfrom [Ru(COD)(methylallyl)₂]:

The entire procedure described herein below is carried out under inert atmosphere. 31.9 mg (0.1 mmol) of [Ru(COD)(methylallyl)₂] were dissolved in 1 ml of CH₂Cl₂, and 0.10 mmol of HBF₄.Et₂O were added to the solution. The solution thus obtained was stirred at room temperature for 2 h, then 45.8 mg (0.2 mmol) of 2-diphenylphosphino ethylamine ((VI)-1) were added and the resulting mixture stirred for 2 h at room temperature.

Preparation in situ of a Ru/(VI)-1 solution from [Ru(C₆H₆)(Cl)₂]₂:

A solution of [RuCl₂(C₆H₆)]₂ (25.0 mg, 0.05 mmol) and (VI)-1 (45.8 mg, 0.20 mmol) in DMF (1.5 ml) was heated to 100° C. for 1 h. The solvent was stripped off in vacuum from the yellow solution, and the residue (yellow solid) taken up in CH₂Cl₂ (0.5 ml).

Hydrogenation:

1.0 μL of one of the above mentioned Ru/(VI)-1 solutions (0.0001 mmol, 10 ppm with respect to the substrate) was added to a solution of the substrate (2.06 g, 10.0 mmol) and t-BuOK (100.8 mg, 0.90 mmol) in i-PrOH (2.20 ml), and the resulting solution exposed to H₂ (40 bar) at 60° with magnetic stirring. The molar proportions correspond to 1 mol of precatalyst per 9000 mol of t-BuOK per 100,000 mol of substrate, {1:9000:100,000}, and the initial concentration of substrate in the i-PrOH was ˜2.4 M. Conversion to 2-ethyl-4-(2′,2′,3′-trimethyl-3′-cyclopenten-1′-yl)-2-buten-1-ol was complete within 3 h.

Further runs were done on the same scale and under the same conditions, but with varying amounts of complex and t-BuOK, and essentially the same results were obtained except for the conversion at very low complex loading. The latter runs, at 1-5 ppm catalyst, relative to the amount of substrate, can be pushed to completion by prolonging the reaction time and/or raising the pressure and/or the temperature. A run with a Ru/(VI)-1/(IV)-1 solution generated in situ has been also performed.

TABLE 3 Hydrogenation of a sandranal using some [RuXY((VI))₂] or [RuXY(VI)(IV)] Conv./ Conv./ Test Complex Com/base time time 1 [RuXY((VI)-1))₂]^(a))* 100/90000 100/3 h 2 [RuXY((VI)-1))₂]^(a))*  5/90000  94/3 h 100/20 h 3 [RuXY((VI)-1))₂]^(a))*  2/90000  34/3 h  88/20 h 4 [RuXY((VI)-1))₂]^(a))*  1/90000  28/3 h  79/20 h 5 [RuCl₂((VI)-1)₂]*** 100/45000 100/1.5 h 6 [RuCl₂((VI)-1)₂]***  10/4500  50/3 h 100/20 h 7 [RuCl₂((VI)-1)₂]***  10/45000 100/1.5 h 8 [RuXY((VI)-1)((IV-4)^(§)]^(a))**  10/45000 100/5 h 9 [RuHCl((VI)-1))₂]^(b))  10/500  97/3 h Sandranal: 2-ethyl-4-(2′,2′,3′-trimethyl-3′-cyclopenten-1′-yl)-2-buten-1-al ^(a))X and Y represent a hydrogen atom or an alkoxy radical ^(b))For comparison, test performed with a complex pre-formed according to the procedure of exemple 1b) Com/base: molar ratio in ppm relative to the substrate Conv./time = conversion (in %, analyzed by GC) of sandranal into the corresponding alcohol at the indicated time in hours.

Ligand (IV)-4 is commercially available from FLUKA. *complex prepared in situ from [Ru(COD)(methylallyl)₂] **complex prepared in situ from [Ru(COD)(methylallyl)₂], according to the procedure herein-above, except that it has been added 0.1 mmol of (VI)-1 and 0.1 mmol (IV)-4 ***complex prepared from [Ru(C₆H₅)(Cl)₂]₂.

EXAMPLE 4 Catalytic Hydrogenation of Some Ketones Using [RuCl₂((VI)-1)₂] Prepared in situ

Using a hydrogenation procedure similar to the one described in example 3. The results are listed in table 4.

TABLE 4 Hydrogenation of a some ketones using [RuCl₂((VI)-1)₂] Test Sub Catalyst: Com/base Conv. 1 1 [RuCl₂((VI)-1)₂]*  10/45000 63 2 1 [RuCl₂((VI)-1)₂]* 10/4500 15 3 2 [RuCl₂((VI)-1)₂]*  10/45000 99 4 2 [RuCl₂((VI)-1)₂]* 10/4500 99 Sub: Substrate: 1 3,3-dimethyl-5-(2′,2′,3′-trimethyl-3′-cyclopenten-1′-yl)-4-penten-2-one; 2 = 4-(2′,6′,6′-trimethyl-1′-cyclohexen-1′-yl)-3-buten-2-one Com/base: molar ratio in ppm relative to the substrate Conv. = conversion (in %, analyzed by GC) of the ketone into the corresponding alcohol after 3 hours. *complex prepared from the [Ru(C₆H₅)(Cl)₂]₂ as in example 3.

EXAMPLE 5 Catalytic Hydrogenation of Imines Using [RuXY((VI))₂] or [RuXY(VI)(IV)]

Under an atmosphere of hydrogen gas (1-3 atm) at room temperature, catalytic amounts of the complexes with a ligand of formula (VI) described in Example 1, together with 5-10 equivalents of KO^(i)Pr effectively and readily catalyzed the hydrogenation of the imine to the corresponding amine. A typical catalytic run using [RuHCl((VI)-1)₂] and N-(1-phenylethylidene)-benzenamine as substrate is as follows:

-   N-(1-phenylethylidene)-benzenamine (4.0 g) and C₆D₆ (1 g) were added     under a flow of hydrogen gas to a Schlenk flask containing     [RuHCl((VI)-1)₂] (105 mg) and KO^(i)Pr (10 mg). The flask was cooled     to liquid nitrogen temperature, filled with H₂ gas, closed and     allowed to gradually warm to room temperature. The mixture was     vigorously stirred for 12 hours. A ¹H NMR spectrum of the reaction     mixture indicated complete conversion of the imine to the amine.     Under these conditions, the complexes reported in Table 5 resulted     in 100% conversion of the imine to the corresponding amine (Table     5).

TABLE 5 Hydrogenation of imines using some [RuXY((VI))₂] or [RuXY(VI)(IV)] Test Sub. Complex Com/base Conv./time 1 1 [RuCl₂((VI)-1))₂] 240/1200 100/<12 h 2 1 [RuCl₂((VI)-2))₂] 2700/13500 100/<4 h 3 1 [RuHCl((VI)-1))₂] 2700/13500 100/<4 h 4 1 [RuHCl((VI)-2)₂] 2700/13500 100/<4 h 5 1 [RuHCl((IV)-2)((VI)-1))] 1700/8500  100/12 h 6 1 [RuHCl((IV)-2)((VI)-2))] 1700/8500  100/12 h 7 1 [RuHCl((IV)-1)((VI)-1))] 1000/5000  100/12 h 8 1 [RuHCl((IV)-3)((VI)-1))] 1000/5000  100/12 h 9 2 [RuCl₂((VI)-1))₂] 1000/5000  100/<8 h 10 2 [RuCl₂((VI)-2))₂] 480/2400 100/<12 h 11 2 [RuCl₂((VI)-3))₂] 1100/5500  100/<24 h 12 2 [RuHCl((VI)-1))₂] 380/1900 100/<12 h 13 2 [RuHCl((VI)-2))₂] 500/2500 100/<12 h 14 2 [RuHCl((IV)-2)((VI)-1))] 1000/5000  100/12 h 15 3 [RuCl₂((VI)-1))₂]* 550/2750 100/<12 h 16 3 [RuCl₂((VI)-2))₂]* 550/2750 100/<12 h 17 3 [RuHCl((VI)-1))₂]* 550/2750 100/<12 h 18 3 [RuHCl((VI)-2)₂]* 550/2750 100/<12 h 19 3 [RuHCl((IV)-2)((VI)-1))]* 1000/5000  100/12 h Sub.: Substrate: 1 = N-(phenylmethylene)-benzenamine, 2 = N-(1-phenylethylidene)-benzenamine, 3 = N-(1-phenylethylidene)-benzenemethanamine Com/base: molar ratio in ppm relative to the substrate Conv./time = conversion (in %, analysed by NMR) of the imine into the corresponding amine at the indicated time in hours. Reaction conditions: H₂ gas (≈3.5 atm.), 20° C. *Hydrogenation of the neat substrate

EXAMPLE 6 Catalytic Hydrogenation of an Aldehyde Using [Ru(V)₂XY] or [Ru(VI)₂XY] Prepared in situ

i) Preparation of the New Ligands of Formula (V) or (VI) Used in the Example

A. 3-(Dicyclohexylphosphino)-1-propylamine ((VI)-4)

10 g (54 mmol) dicyclohexylphosphine, 3.1 g (54 mmol) allylamine and 0.2 g ditertiobutylperoxide were stirred under nitrogen in an autoclave for 2 hours at 150° C. The resulting mixture was fractionnated by vacuum distillation to give the desired aminophosphine (colorless liquid) in 92% purity and 50% yield.

¹³C-NMR (CDCl₃): 43.6 (t, CH₂—NH₂); 33.4-33.3 (d, P—CH cyclohexyl); 33.4-18.3 (t, cyclohexyl)

MS (relative intensities): 255(M+, 0.6), 172(100), 130(54.7), 131(39.8), 90(35.1).

B. 2-[2-(Diisobutylphosphino)-ethyl]pyridine ((V)-1)

10 g (68 mmol) diisobutylphosphine, 7.1 g (68 mmol) 2-vinyl pyridine and 0.1 g 2,2′-azobis(isobutyronitrile) (AIBN, VAZO® 64) were stirred under nitrogen in a glass reactor for 2 hours at 85° C. The resulting mixture was fractionated by vacuum distillation to give the desired aminophosphine (colourless liquid) in 95% purity and 60% yield.

¹³C-NMR (CDCl₃): 160.4(s, ═C—N Py); 149.3-122.9 (d, Py ring); 30.3 (t, CH₂-Py); 28.9 (t, P—CH₂CH₂-Py); 38.5 (t, PCH₂ iBu)

³¹P {¹H} NMR (CDCl₃): 45.66 ppm.

MS (relative intensities): 194(100), 138(47), 136(15.6), 195(13.5).

C. 2-[2-Diisobutylphosphino)-ethyl]-1H-Imidazole ((V)-2)

10 g (68 mmol) diisobutylphosphine, 6.4 g (68 mmol) 1-vinyl imidazole and 0.1 g 2,2′-azobis(isobutyronitrile) (AIBN, VAZO® 64) were stirred under nitrogen in a glass reactor for 2 hours at 85° C. The resulting mixture was fractionated by vacuum distillation to give the desired aminophosphine (colourless liquid) in 96% purity and 50% yield.

¹³C-NMR (CDCl₃): 136.7, 129.5, 118.5 (d, Im); 44.8 (t, C—N Im); 31.2 (t, P—CH₂CH₂-Im) 38.9 (t, PCH₂ iBu).

MS (relative intensities): 240(M+,100), 239(89), 128(91), 95(90).

ii) Preparation in situ of a Ru/(ligand) solution from [Ru(COD)(methylallyl)₂]

The whole procedure described herebelow is carried out under inert atmosphere. 31.9 mg (0.1 mmol) of [Ru(COD)(methylallyl)₂] were dissolved in 1 ml of CH₂Cl₂, and 0.10 mmol of HBF₄.Et₂O were added to the solution. The solution thus obtained was stirred at room temperature for 2 h, then 0.2 mmol of the desired ligand were added and the resulting mixture stirred for 2 h at room temperature. Finally, to the resulting solution were added 9 ml of CH₂Cl₂.

iii) Hydrogenation

In a Schlenk tube, in a glove box under inert atmosphere, an appropriate quantity of sodium methoxide, according to Table 6 or 7 (column A), was dissolved in an appropriate quantity of iso-propanol, according to Table 6 or 7 (column B). Then an appropriate quantity of Sandranal, according to Table 6 or 7 (column B), was added and the mixture was stirred for 5 minutes. To the resulting solution was added an appropriate volume of the Ru/(ligand) solution, according to Table 6 or 7 (column C), the latter being obtained as in here-in-above using the desired ligand. After 10 minutes stirring the solution was transferred into a bomb wherein solution was warmed at 40° C. and left under 30 atm. of H₂. The reaction was followed by GC, and once the starting product has disappeared the reaction was cooled to room temperature and the pressure lowered to 1 atm.

The ligand structure, the quantities and results for each test is summarized in Table 6 or 7.

TABLE 6 Hydrogenation of Sandranal using a Ru complex with ligands of formula (V) Test Complex A B C Com/base Conv./time 1 [RuXY((V)-1))₂]^(a)) 0.3 25.75 1 80/44000 86/16 h 2 [RuXY((V)-2))₂]^(a)) 0.3 25.75 1 80/44000 64/16 h

TABLE 7 Hydrogenation of Sandranal using a Ru complex with ligands of formula (VI) Conv./ Test Complex A B C Com/base time 1 [RuXY((VI)-4))₂]^(a)) 0.3 25.75 1 80/44000 74/8 h 2 [RuXY((VI)-4))₂]^(a)) 0.3 25.75 0.5 40/44000 78/20 h 3 [RuXY((VI)-4))₂]^(a)) 0.3 25.75 0.25 20/44000 80/24 h 4 [RuXY((VI)-1))₂]^(a)) 0.6 103 0.5 10/22000 95/6 h  5* [RuXY((VI)-5))₂]^(a)) 1.2 103 0.5 10/45000 91/7 h ^(a))X and Y represent a hydrogen atom or an alkoxy radical Sandranal: 2-ethyl-4-(2′,2′,3′-trimethyl-3′-cyclopenten-1′-yl)-2-buten-1-al Com/base: molar ratio in ppm relative to the substrate Conv./time = conversion (in %, analyzed by GC) of the aldehyde into the corresponding alcohol at the indicated time in hours.

A = grams of NaOMe used in the test B = grams of ^(i)PrOH used in the test; grams of Sandranal used in the test C = volume (in ml) of the Ru/(V) or Ru/(VI) solution used in the test

EXAMPLE 7 Catalytic Hydrogenation of Ketones Using [RuXY((V′))₂]

TABLE 8 Structure of the ligands of formula (V′) used for the synthesis of the corresponding complexes structure name

(V′)-1

(V′)-2

(V′)-3

(V′)-4 Ligands (V′)-1 and (V′)-2 are commercially available from STREM. Ligands (V′)-3 and (V′)-4 were obtained from the corresponding amine according the method described by Gao et al. in Polyhedron 1996, 15, 1241 Preparation of the Complex [RuCl₂((V)-1)₂]:

This complex has been obtained by reacting (V′)-1 (562 mg, 1.408 mmole) and [RuCl₂(DMSO)₄] (341 mg, 0.616 mmole) in refluxing toluene (20 ml) under stirring for 8 hour, during which an orange precipitate is formed. After cooling at room temperature, the solid was filtered washed with cold toluene and then with hexane and finally dried under vacuum. 376 mg of [RuCl₂((V′)-1)₂] were obtained (yield 66%).

³¹P{¹H} NMR (CD₂Cl₂): 60.7 ppm (s).

Preparation of the Complex [RuCl₂((V′)-2)₂]:

This complex has been obtained by reacting (V′)-2 (255 mg, 0.580 mmole) and [RuCl₂(PPh₃)₃] (270 mg, 0.282 mmole) in toluene (20 ml) during 30 min at room temperature. Then the solution was refluxed for 8 hour and next the resulting red-purple solution cooled at room temperature. After a small amount of solid was removed by filtration, then the resulting solution was concentrated to 5 ml and the product precipitated by adding 100 ml of pentane and the suspension stirred for 2 hours. Finally, the precipitate was collected by filtration, washed with pentane and dried under vacuum. 300 mg of [RuCl₂((V′)-2)₂] were obtained (yield=100%)

¹H NMR (CD₂Cl₂): Aromatic protons between 6.2 and 9.2 ppm.

³¹P {¹H} NMR (CD₂Cl₂): 49.6 ppm (s).

Preparation of the Complex [RuCl₂((V)-3)₂]:

This complex has been obtained by reacting (V′)-3 (190 mg, 0.529 mmole) and [RuCl₂(PPh₃)₃] (221 mg, 0.231 mmole) in CH₂Cl₂ (10 mL) for 18 hours at room The resulting red solution was concentrated to 1 ml and the product was precipitated by adding 50 ml of pentane and stirring for 2 hours. Finally, the precipitate was collected by filtration, washed with pentane and dried under vacuum. 160 mg of red orange [RuCl₂((V′)-3)₂] were obtained (yield=78%)

¹³C NMR (CD₂Cl₂): N—CH₂ at 66.7 ppm; N—CH₂—CH₂ at 41.5 ppm; CH(CH₃)₂ at 26.8 ppm; CH₃ at 22.5 and 23.1 ppm; N═CH at 168.8 ppm, aromatic protons between 127 and 140 ppm.

³¹P {¹H} NMR (CD₂Cl₂): 52.6 ppm (s).

Preparation of the Complex [RuCl₂((V)-4)₂]:

This complex has been obtained by reacting (V′)-4 (225 mg, 0.529 mmole) and [RuCl₂(PPh₃)₃] (230 mg, 0.240 mmole) in CH₂Cl₂ (10 ml) for 3 days at room temperature. The resulting solution was concentrated to 1 ml, the product was precipitated by adding 50 ml of pentane and the suspention stirred for 2 hours. Finally, the precipitate was collected by filtration, washed with pentane and dried under vacuum. 140 mg of [RuCl₂((V′)-3)₂] were obtained (yield=60%)

¹H NMR (CD₂Cl₂): Aliphatics protons between e 0.6 and 5.2 ppm, Aromatic protons between 6.2 and 7.5 ppm, N═CH at 8.15 ppm (AB system).

¹³C NMR (CD₂Cl₂): Aliphatic carbons between 14 and 76 ppm (20 signals, all of the carbons give two resonances), Aromatic protons between 127 and 140 ppm, N═CH at 168.2 and 169.1 ppm.

³¹P {¹H} NMR (CD₂Cl₂): 52.7 ppm (AB system).

Hydrogenation a Substrate to the Corresponding Alcohol

An aliquot of a 2.1 M solution of substrate in ^(i)PrOH, representing 20 mmoles of said substrate, the desired amount of ^(t)BuOK were introduced into an autoclave and stirred until complete dissolution of the base. Afterward, to said solution was added an adequate amount of a stock solution of the desired complex dissolved in CH₂Cl₂ (typical metal concentration is 0.02 M). Then, the autoclave was purged 3 times with H₂, and finally warmed at 60° C. under 45 bar of H₂. The reaction was followed by GC, and once the starting product has disappeared the reaction mixture was cooled to room temperature and the pressure lowered to 1 atm. The results are summarized in the Table 9.

TABLE 9 Hydrogenation of a substrate using some complexes [RuXY((V′))₂] Test Sub. Complex Com/base Conv./time 1 1 [RuCl₂((V′)-1)₂] 10/4500 12/24 h 2 1 [RuCl₂((V′)-1)₂]  10/45000 27/24 h 3 1 [RuCl₂((V′)-2)₂] 10/4500  9/24 h 4 1 [RuCl₂((V′)-2)₂]  10/45000 28/24 h 5 2 [RuCl₂((V′)-2)₂] 100/45000  7/24 h 6 2 [RuCl₂((V′)-2)₂]  100/450000 21/24 h 7 1 [RuCl₂((V′)-3)₂] 10/4500 45/24 h 8 1 [RuCl₂((V′)-3)₂]  10/45000 100/6 h  9 1 [RuCl₂((V′)-4)₂] 10/4500 68/24 h 10 1 [RuCl₂((V′)-4)₂]  10/45000 100/24 h  Sub. = substrate, 1 = acetophenone, 2 = 3,3-dimethyl-5-(2′,2′,3′-trimethyl-3′-cyclopenten-1′-yl)-4-penten-2-one. Com/base: molar ratio in ppm relative to the substrate Conv./time = conversion (in %, analyzed by GC) of the substrate into the corresponding alcohol at the indicated time in hours

EXAMPLE 8 Catalytic Hydrogenation of Acetophenone Using Some [RuXY((VI)-1)₂] without Addition of a Base

Under an atmosphere of hydrogen gas (40 atm) at 60° C., catalytic amounts of [RuHCl((Vl)-1)₂] described in Example 1, readily catalyzed the hydrogenation of acetophenone to phenylethanol without the addition of a base. A typical catalytic run for a catalyst/substrate (c/s) ratio of 10 ppm and using [RuHCl((VI)-1)₂] is as follows:

-   In a Schlenk flask, under Ar and at ambient temperature,     [RuHCl((VI)-1)₂] (12 mg, 0.02 mmol), (as obtained in example 1b),     was suspended in i-PrOH (1 ml), and the resulting suspension stirred     for ca. 5 min. 20 μl (0.0004 mmol) of the finely dispersed     light-yellow suspension of [RuHCl((VI)-1)₂] were added to a solution     of acetophenone (4.80 g, 40 mmol) in i-PrOH (14.4 ml) that had been     charged into a autoclave under Ar. The autoclave was sealed and     pressurised with 40 bar of H₂, and its contents stirred and heated     to 60° C. Samples for analysis by GC were periodically withdrawn,     and the reaction times and the results are given in the Table 10.

TABLE 10 Hydrogenation of acetophenone using [RuHCl((VI)-1)₂] without base Test Complex Com Conv./time Conv./time 1 [RuHCl((VI)-1)₂] 100 100/10 m 2 [RuHCl((VI)-1)₂] 10  70/45 m 100/3 h  3 [RuHCl((VI)-1)₂] 2  93/4 h 4 [RuHCl((VI)-1)₂]* 100  8/20 h 5 [Ru(AcO)₂((VI)-1)₂] 100  65/3 h 100/20 h 6 [Ru(AcO)₂((VI)-1)₂] 10 100/20 h Com: molar ratio in ppm relative to the substrate Conv./time = conversion (in %, analyzed by GC) of the substrate into the corresponding alcohol at the indicated time in hours (h) or in minute (m) *for comparison, test performed with the same experimental procedure but without H₂ gas (reduction by hydrogen transfer) 

1. A complex of formula (II): [Ru(L)₁(L′)₁XY]  (II) wherein: X and Y represent, simultaneously or independently, a hydrogen or chlorine atom, a methoxy, ethoxy or isopropoxy radical, or a CH₃COO or CH₃CH₂COO radical; L′ represents a bidentate P-P ligand of formula

wherein R² and R³ represent a linear, branched or cyclic C₂ to C₆ alkyl group or an aromatic ring, possibly substituted, and Q represents the butane-1,4-diyl radical, possibly substituted, a ferrocenediyl or a binaphthyldiyl radical, possibly substituted; the possible substituents of the Q group are C₁ to C₅ alkoxy or polyalkyleneglycol groups, C₁ to C₄ alkyl groups, or C₅ to C₁₀ cycloalkyl or aromatic groups; and L is a ligand of formula (V), (V′), (VI), or (VI′)

wherein: the dotted lines in formula (V′) or (VI′) indicate the presence of a phenyl or a naphthyl group; G′ represents a R⁶C═NR¹ group or a C═N function-containing heterocycle, possibly substituted and possibly containing other heteroatoms; R¹ represents a hydrogen atom or a C₁ to C₄ linear or branched alkyl group, possibly substituted; R² and R³ are as defined above; b represents 1 or 2; R⁶ and R⁷ represent, simultaneously or independently, a hydrogen atom, a linear or branched C₁ to C₄ alkyl group, possibly substituted, or an aromatic ring possibly substituted; or R⁶ and R¹ may optionally be bonded together to form a saturated heterocycle, possibly substituted and possibly containing other heteroatoms; the possible substituents of R¹ to R³, R⁶ and R⁷ are C₁ to C₅ alkoxy or polyalkyleneglycol groups, C₁ to C₄ alkyl groups, C₅ to C₁₀ cycloalkyl or aromatic groups.
 2. The complex of claim 1, wherein L is a ligand of formula (V) or (V′)

and R² and R³ represent a linear, branched or cyclic C₂ to C₆ alkyl group or an aromatic ring, possibly substituted; and R⁶ represents a hydrogen atom, a linear or branched C₁ to C₄ alkyl group, possibly substituted, or an aromatic ring, possibly substituted.
 3. The complex of claim 1 wherein L is a ligand of formula (VI), or (VI′)


4. The complex of formula (II) of claim 1, wherein X represents a hydrogen atom and Y represents a hydrogen or chlorine atom, a methoxy, ethoxy or isopropoxy radical, or a CH₃COO or CH₃CH₂COO radical.
 5. The complex of formula (II) of claim 1, wherein X and Y represent a hydrogen atom or a CH₃COO or CH₃CH₂COO radical.
 6. The complex of claim 1 wherein L is a ligand of formula (V) or (VI).
 7. A complex of formula (II): [Ru(L)₁(L′)₁XY]  (II) wherein: X and Y represent, simultaneously or independently, a methoxy, ethoxy or isopropoxy radical, or a CH₃COO or CH₃CH₂COO radical; L′represents a bidentate P-P ligand of formula

wherein R² and R³ represent a linear, branched or cyclic C₂ to C₆ alkyl group or an aromatic ring, possibly substituted, and Q represents the butane-1,4-diyl radical, possibly substituted, a ferrocenediyl or a binaphthyldiyl radical, possibly substituted; the possible substituents of the Q group are C₁ to C₅ alkoxy or polyalkyleneglycol groups, C₁ to C₄ alkyl groups, or C₅ to C₁₀ cycloalkyl or aromatic groups; and L is a ligand of formula (V), (V′), (VI), or (VI′)

wherein: the dotted lines in formula (V′) or (VI′) indicate the presence of a phenyl or a naphthyl group; G′represents a R⁶C═NR¹ group or a C═N function-containing heterocycle, possibly substituted and possibly containing other heteroatoms; R¹ represents a hydrogen atom or a C₁ to C₄ linear or branched alkyl group, possibly substituted; R² and R³ are as defined above; b represents 1 or 2; Rand R⁷ represent, simultaneously or independently, a hydrogen atom, a linear or branched C₁ to C₄ alkyl group, possibly substituted, or an aromatic ring possibly substituted; or R⁶ and R¹ may optionally be bonded together to form a saturated heterocycle, possibly substituted and possibly containing other heteroatoms; the possible substituents of R¹ to R³, R⁶ and R⁷ are C₁ to C₅ alkoxy or polyalkyleneglycol groups, C₁ to C₄ alkyl groups, C₅ to C₁₀ cycloalkyl or aromatic groups.
 8. The complex of claim 7, wherein L is a ligand of formula (V) or (V′)

and R² and R³ represent a linear, branched or cyclic C₂ to C₆ alkyl group or an aromatic ring, possibly substituted; and R⁶ represents a hydrogen atom, a linear or branched C₁ to C₄ alkyl group, possibly substituted, or an aromatic ring, possibly substituted.
 9. The complex of claim 7, wherein L is a ligand of formula (VI) or (VI′).
 10. The complex of claim 7, wherein L is a ligand of formula (V) or (VI). 